Apparent fusion of basement membranes in colorectal carcinoma

Previous studies on colorectal carcinomas indicate that consistent differences in epithelial basement membrane (EBM) integrity are present between the tumour centre and periphery. We report that within the tumour centre, EBM staining between back-to-back (BTB) neoplastic glands (i.e., adjacent glands in direct contact with no intervening connective tissue) generally follows a pattern different from that of EBM staining at the tumour:stromal interface (TSI). Such distinctions are important, since the factors responsible for EBM deficiencies may vary with intra-tumoural location, as may the prognostic significance of these deficiencies. Analysis of paraffin sections from 130 colorectal carcinoma cases showed that EBM staining between BTB glands is generally weaker and more discontinuous than at the TSI, sometimes appearing as a linear array of immunostained granules on high-resolution light microscopy. By double-labelling immunofluorescence analysis of cryostat sections from 30 cases, a decrease in type-IV collagen:laminin staining intensity ratio was found between BTB glands. Hence, the composition of EBM between BTB glands appears to be abnormal. As much recent evidence indicates that epithelial:mesenchymal interactions play an essential role in EBM formation, the demonstration of immunostained EBM fragments between BTB glands requires an explanation: We suggest that the synthesis of EBM between BTB glands involved previously intervening stromal (mesenchymal) cells, and that EBM fusion and dissolution occur between BTB glands following the displacement of these cells.